Prader–Willi syndrome and autism spectrum disorders: an evolving story

Prader–Willi syndrome (PWS) is well-known for its genetic and phenotypic complexities. Caused by a lack of paternally derived imprinted material on chromosome 15q11–q13, individuals with PWS have mild to moderate intellectual disabilities, repetitive and compulsive behaviors, skin picking, tantrums, irritability, hyperphagia, and increased risks of obesity. Many individuals also have co-occurring autism spectrum disorders (ASDs), psychosis, and mood disorders. Although the PWS 15q11–q13 region confers risks for autism, relatively few studies have assessed autism symptoms in PWS or directly compared social, behavioral, and cognitive functioning across groups with autism or PWS. This article identifies areas of phenotypic overlap and difference between PWS and ASD in core autism symptoms and in such comorbidities as psychiatric disorders, and dysregulated sleep and eating. Though future studies are needed, PWS provides a promising alternative lens into specific symptoms and comorbidities of autism

Long-term outcome of chronic dialysis in children

As the prevalence of children on renal replacement therapy (RRT) increases world wide and such therapy comprises at least 2% of any national dialysis or transplant programme, it is essential that paediatric nephrologists are able to advise families on the possible outcome for their child on dialysis. Most children start dialysis with the expectation that successful renal transplantation is an achievable goal and will provide the best survival and quality of life. However, some will require long-term dialysis or may return intermittently to dialysis during the course of their chronic kidney disease (CKD). This article reviews the available outcome data for children on chronic dialysis as well as extrapolating data from the larger adult dialysis experience to inform our paediatric practice. The multiple factors that may influence outcome, and, particularly, those that can potentially be modified, are discussed

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

Autism spectrum disorders: an overview on diagnosis and treatment

Pervasive developmental disorders are now commonly referred to as autism spectrum disorders (ASDs). ASDs present with a range of severity and impairments, and often are a cause of severe disability, representing a major public health concern. The diagnostic criteria require delays or abnormal functioning in social interaction, language, and/or imaginative play within the first 3 years of life, resulting in a deviation from the developmental pattern expected for the age. Because establishing a diagnosis of ASD is possible as early as 18-24 months of age, clinicians should strive to identify and begin intervention in children with ASD as soon as signs are manifest. Increasing efforts are underway to make ASD screening universal in pediatric healthcare. Given the crucial importance of early identification and multiple modalities of treatment for ASD, this review will summarize the diagnostic criteria, key areas for assessment by clinicians, specific scales and instruments for assessment, and discussion of evidence-based treatment programs and the role of specific drug therapies for symptom management.Universidade de São Paulo School of Medicine Department of PsychiatryUSP School of Medicine Institute of PsychiatryUniversidade Federal de São Paulo (UNIFESP) Department of Psychiatry Child and Adolescent Psychiatry UnitUniversidade Presbiteriana Mackenzie Health and Biological Science Center Graduate Program in Development DisordersUniversity of California Department of Psychiatry and Biobehavioral SciencesUNIFESP, Department of Psychiatry Child and Adolescent Psychiatry UnitSciEL

Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development

OBJECTIVES: To compare GI problems among children with: 1) autism spectrum disorder (ASD), 2) developmental delay (DD) and 3) typical development (TD). METHODS: In 960 children from the CHildhood Autism Risks from Genetics and the Environment (CHARGE) study, we assessed GI symptom frequency. We examined scores on five Aberrant Behavior Checklist subscales comparing ASD children with high vs. low frequency GI symptoms. RESULTS: Compared to TD children, those with ASD (aOR 7.92[4.89–12.85]) and DD (aOR 4.55 [2.51–8.24]) were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on Irritability, Social Withdrawal, Stereotypy, and Hyperactivity compared with children having no frequent GI symptoms. CONCLUSIONS: Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention

Supernumerary (B) chromosomes in populations of Picea abies (L.) H. Karst. from Western Rhodopes (Bulgaria)

Investigations on B chromosomes found for the first time for Picea abies (L.) H. Karst. have been conducted. Seeds of Picea abies from two populations of Western Rhodopes (Bulgaria) located at the southern border of species range, and protected according to Bern Convention and EC Habitat Directive were collected for this study. Mixoploidy was detected in some germinating seeds of Picea abies. It was found that metaphase cells of germinating seeds contain 0–4 B chromosomes of both metacentric and submetacentric types. The variability of B chromosomes number and their occurrence was observed. Along with B chromosomes, some chromosome aberrations such as fragments and ring chromosomes were revealed in metaphase cells of Picea abies from studied populations. The possible adaptive role of B chromosomes presence for Picea spp. is discussed.Проведено исследование В-хромосом, обнаруженных впервые у вида Picea abies (L.) H. Karst. Для настоящего исследования семена собраны из двух популяций Picea abies в Западных Родопах (Болгария), расположенных на южной границе видового ареала и охраняемых в соответствии с Бернской конвенцией и Директивой ЕС о местообитаниях. В отдельных проростках семян Picea abies найдена миксоплоидия. Обнаружено, что метафазные клетки проростков семян из изученных популяций Picea abies содержат 0–4 В-хромосомы как метацентрического, так и субметацентрического типов. Наблюдается изменчивость числа В-хромосом и их появления. Наряду с В-хромосомами в метафазных клетках Picea abies выявлены хромосомные мутации – фрагменты и кольцевые хромосомы. Обсуждается возможная адаптивная роль присутствия В-хромосом у видов Picea.Проведено дослідження В-хромосом, виявлених вперше у виду Picea abies (L.) H. Karst. Для даного дослідження насіння зібране з двох популяцій Picea abies в Західних Родопах (Болгария), що розташовані на південному кордоні видового ареалу та охороняються відповідно до Бернської конвенції та Директивою ЄС про місце розповсюдження. В окремих проростках насіння Picea abies знайдено міксоплоїдію. Виявлено, що метафазні клітини проростків насіння з вивчених популяцій Picea abies містять 0–4 В-хромосоми як метацентричного, так і субметацентричного типів. Спостерігається мінливість числа В-хромосом. Поряд з В-хромосомами у метафазних клітинах Picea abies виявлено хромосомні мутації – фрагменти та кільцеві хромосоми. Обговорюється можлива адаптивна роль присутності В-хромосом у видів Picea